Healing powder and method of use thereof

ABSTRACT

A wound healing powder, comprising a sugar selected from the group consisting of one or more pharmaceutically acceptable monosaccharides and disaccharides, in an amount of at least 25% by weight of the powder mixture; and an absorbent agent which forms a bioabsorbable biocompatible matrix with wound secretions, comprising a polymer formed of one or more of saccharide or saccharide derivative monomers and lactic acid monomers, in an amount of at least 25% by weight of the powder mixture.

RELATED APPLICATIONS

The present application is a Continuation of U.S. patent applicationSer. No. 11/938,147, filed Nov. 9, 2007, now U.S. Pat. No. 8,252,335,issued Aug. 28, 2012, which is a continuation of U.S. patent applicationSer. No. 11/385,265, filed Mar. 21, 2006, now U.S. Pat. No. 7,294,350,the entirety of which is expressly incorporated herein by reference.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to the field of wound dressings, and moreparticularly to powders which assist in wound healing.

2. Prior Art

Cornstarch has been known as a soothing and drying agent for irritatedskin, such as diaper rash. Cornstarch is a dextrin, and containsamylase.

The Dressings Times, Vol. 3, No. 2, discusses wound dressings whichemploy sugar pastes. (www.smtl.co.uk/WMPRC/DressingsTimes/vol3.2.txt).It reports that, in 1976, Herszage and Montenegro of Argentina usedordinary sugar to treat the wounds of two patients with post-surgicalnecrotic cellulitis. Further successes followed and in 1980 theyreported on the use of sugar paste in 120 infected wounds and recorded acure rate of 99.2%.[1] The time taken for the wounds to heal variedbetween 9 days and 17 weeks, but it was observed that odor and secretionbegan to diminish within 24 hours and disappeared totally after 72 to 96hours of treatment. In 1985, Trouillet et al[2] described the use ofsugar in the treatment of 19 patients with acute mediastinitis followingcardiac surgery. Wounds were packed every 3 to 4 hours with ordinarycommercially available granular sugar (sucrose). The authors noted nearcomplete debridement followed by the rapid formation of granulationtissue and eradication of bacterial infection after an average of 7.6days of treatment.

Sugar was first used as a dressing in Northwick Park Hospital in 1982when it was placed into infected radical vulvectomy wounds that had notresponded to more conventional therapies. However, due to the nature ofsuch wounds, packing with granular sugar was found to be impossible andtherefore a thick paste was developed. Other early patients to betreated with sugar at Northwick Park were two hypo-gammaglobulinaemicindividuals who had developed extensive tracking sinuses. For these, athin paste was formulated that could be injected into the narrow wounds.

Thick sugar paste has a consistency similar to that of modeling clay andcan be molded in the gloved hand immediately prior to packing intocavities with large openings such as pressure sores. Thin sugar pasteresembles thin honey; it is suitable for instillation into cavities withsmall openings with a syringe and fine plastic tube or catheter.

Formulae for sugar pastes (Prior Art) Thin Thick Caster sugar 1200 g1200 g (fine granular sucrose) Icing sugar - additive free 1800 g 1800 g(powdered sucrose) Polyethylene glycol 400 1416 ml 686 ml HydrogenPeroxide 30% 23.1 ml 19 ml (Final concentration of hydrogen peroxide is0.15% v/w.)

The pastes are prepared in the hospital pharmacy by combining the H₂O₂with the PEG 400 and then incorporating this solution into the sugarswith the aid of a mechanical mixer.

When homogenous the paste is packed into screw capped plastic containersand stored at 4 C. The pastes are chemically stable for at least 6months from preparation.

Polyethylene glycol (PEG) 400 was chosen as the lubricant because itdoes not interact with other components of the paste and is used in avariety of pharmaceutical preparations. It is a synthetic polymer thatis also used in the cosmetic industry and has significant anti-bacterialproperties. [3][4] Polyethylene glycol 400 can be absorbed from mucousmembranes and high blood levels may be nephrotoxic.[5] Although no toxiceffects have been noted in our patients, many of whom are elderly andfrail, sugar paste should be used with care in patients with impairedrenal function as any absorbed polyethylene glycol is excreted renally.

Sugar paste has been used on most wound types but it has been found tobe particularly effective for treating infected and malodorous wounds.Twice daily application are advised to provide the optimum antibacterialeffect. This has been demonstrated both in patients with malodorouswounds (when the smell of infected necrotic tissue is removed after 2-3days), and in patients with infected abscesses. Irrigation with thinsugar paste has achieved successful results in patients with chronicdischarging sinuses who had previously failed to respond to othertherapies. Repeated application over 3 to 6 weeks is generally requiredto bring about complete healing. Sugar paste lowers the pH of wounds toapproximately 5 which may be important in infected wound although thepaste does not stimulate or retard granulation tissue formation in cleanwounds in the pig model.[6]

Sugar paste (thick and thin) is rapidly bactericidal against allorganisms so far tested when challenged according to a modified BritishPharmacopoeia antimicrobial preservatives effectiveness test. Whensamples of the paste were inoculated with Staphylococcus aureus,Streptococcus faecalis, Escherichia coli or Candida albicans, to give10⁵ cfu/gram, less than 10 cfu/gram were detectable after 1 hour at 25C.[7] Pastes diluted with serum have a reduced bactericidal effect −75%paste in serum gave an 80% reduction in viable numbers of S. aureuswithin 2 hours and a 99% reduction in viable numbers of Proteusmirabilis within 1 hour[3].

Although the application of sugar to a wound creates an environment withlow water activity (aw) and high osmotic pressure, overall the woundremains moist. (The water activity of a solution is the ratio of itswater vapour pressure to that of pure water at the same temperature sothat aw=P/Po).

The effect of reducing water activity values on the growth of bacteriahas been investigated by Chirife et al[8] who determined the limitingwater activities at which different species of bacteria will grow. Wehave determined the water activity of our pastes, at different dilutionsin serum, by measuring water vapour pressure at 25 C with an electronichygrometer. Undiluted pastes have an almost zero availability of waterbecause the sugar (sucrose) is dispersed in Polyethylene glycol 400which does not contain water. Sugar has an osmotic action which can bethermodynamically related to water activity by the followingequation:[8]

O=(RT/V)×log(1/aw),

where 0 is the osmotic pressure,

R is the gas constant,

T is the absolute temperature in degrees Kelvin,

V is the partial molal volume of water, and

aw is the water activity.

Thus, by determining water activity, the osmotic pressure can becalculated. From this equation it will be seen that a solution of lowwater activity has high osmotic pressure.

Because of the difficulty of conducting a controlled trial of sugarpaste in human wounds, an animal study has been conducted[6] using amethod similar to that reported by Winter and Scales.[9] Full thicknesswounds 25 mm square, and 9 mm deep were made in the backs of pigs andaround each was placed a colostomy stoma ring. This in turn was coveredwith a semipermeable plastic film dressing (Opsite) so as to form amoist chamber. Wounds were either covered with Opsite alone, or packedwith thick sugar paste or cotton gauze soaked in various antisepticsolutions and then covered in Opsite. The results showed that there wasno significant difference between wounds left unpacked, but covered withOpsite, and those Opsite covered wounds packed with sugar paste,indicating that although sugar paste did not stimulate the formation ofgranulation tissue, neither did it cause inhibition or toxicity.However, all wounds packed with antiseptics showed evidence of delayedhealing, especially those containing chlorhexidine gluconate 0.2%. Thepig model wounds were not infected so no conclusions can be drawn on therelative value of Opsite and sugar paste for healing infected wounds.

Dressing Times concluded that sugar paste should be considered for themanagement of all infected and malodorous wounds. It is a far lessexpensive alternative to Debrisan and similar products which are ofdubious efficacy and are often difficult to remove from wounds. Sugarpaste was also considered superior to charcoal dressings for treatingmalodorous wounds as it removes the cause of the smell and in thisrespect is similar to metronidazole gel. However sugar paste may bepreferable to metronidazole gel for treating such wounds as the use oftopical antibacterials and antibiotics should be avoided.[10]

Sugar paste lacks the toxicity of most antiseptics and it does notdisrupt the architecture of the healing wounds, as does packing withgauze.

The paste is self-sterilizing and can be produced in differentviscosities to suit all kinds of wound and it is not painful to apply.It may cause bleeding when granulation tissue is well formed, at whichstage simple, non-impregnated dressings should be applied which willkeep the wound moist and allow epithelialisation to occur.

REFERENCES

-   1. Herszage L. et al., Tratamiento de las heridas supuradas con    azucar granulado comercial, Biol Trab Soc Argent., 1980, 41,    315-330.-   2. Trouillet J. L., et al., Use of granulated sugar in treatment of    open mediastinitis after cardiac surgery, Lancet, 1985, 2, 180-183.-   3. Ambrose U. An investigation into the mode of action of Northwick    Park Hospital sugar pastes. Hatfield Polytechnic, 1986, B.Sc.    Applied Biology Thesis.-   4. Chirife J., et al., In-vitro antibacterial activity of    concentrated polyethylene glycol 400 solutions, Antimicrob. Ag.    Chemother., 1983, 24, 409-412.-   5. Wilson C. G. and Thomas N. W. Interaction of tissues with    polyethylene glycol vehicles Pharm. Int., 1984, 5 94-97.-   6. Archer H. G. et al., A controlled model of moist wound healing:    comparison between semi-permeable film, antiseptics and sugar    paste. J. exp. Path., 1990, 75, 155-170.-   7. Gordon H., et al., Sugar and wound healing Lancet, 1985, 2,    663-664.-   8. Chirife J., et al., In-vitro study of bacterial growth inhibition    in concentrated sugar solutions: microbiological basis for the use    of sugar in treating infected wounds, Antimicrob. Ag. Chemother.    1983, 23, 766-773.-   9. Winter G. D. and Scales J. T. Effect of air drying and dressings    on the surface of a wound Nature, 1963, 197, 91-92.-   10. Morgan D. Formulary of Wound Management Products (3^(rd)    edition), 1989, Clwyd Health Authority, Preswylfa, Hendy Road, Mold,    Clwyd CH₇ ₁PZ.

DESCRIPTION OF THE INVENTION

The present invention comprises a wound dressing for application to skinand mucous membranes, comprising at least 25% starch or polylactic acidand at least 25% of a mono- or disaccharide sugar, with a remaindercomprising a compatible pharmaceutically acceptable formulation.

The resulting product is a powder which, when applied to a wound,absorbs wound secretions and acts as an antibacterial, likely due to theaction of a high concentration of sugar. The product promotes healing,and aids in tissue regeneration. The power is applied to a wound insufficient quantities to cake on the surface, forming a self-adherentdressing. The starch component acts as a matrix for tissue regeneration.

The product can be provided as a free powder, to be applied directly toa wound, or in the case of anal fissures and proctitis, the like, as acapsule containing the powder. The capsule is, for example, a standardgelatin capsule.

The starch may be, for example, cornstarch, which contains amylase andamylopectin, or other polysaccharides.

The starch may also be formed of saccharide monomer derivatives, such assulfonated, acetylated, and other known biocompatible derivatives ofsaccharide monomers which form biocompatible polymers.

The disaccharide and polysaccharide (and/or polylactose) combinationincreases the blood flow within the tissues, which is important fortissue regeneration and aids in promoting a functional microvasculature,and ultimately, successful healing. A preferred sugar component is 10×powdered (confectioner's) sugar (sucrose).

The powder can be applied to various kinds of wounds, including ulcers,burns, avulsions, lacerations, surgical excisions, pilonodal cysts, andthe like.

The powder is applied to wounds as necessary to absorb the secretions,for example at least twice daily. In a number of tests, with healing isvisibly promoted within three days, and complete healing is generallyobserved within 7-10 days. In the case of open wounds, e.g., pilonidaloperations, a longer period of treatment may be necessary.

In the case of a rectal suppository, the capsule is inserted in therectum after bowel movements, and at least twice daily.

A dressing may be placed over the powder, for example a Telfa dressing.Telfa consists of a thin layer of absorbent cotton fibers, enclosed in asleeve of poly(ethylene terephthalate) that is perforated in a regularpattern and sealed along two edges. The plastic film is present toprevent the dressing adhering to the surface of the wound, and isperforated to allow the passage of exudate from the wound into the bodyof the pad.

According to the present invention, since the starch absorbs thesecretions, the body of the pad serves only a secondary function, andthe combined dressing may be used on wounds which produce secretionswhich would normally be contraindicated for Telfa® alone.

It is therefore an object of the invention to provide a wound healingpowder, comprising a sugar selected from the group consisting of one ormore pharmaceutically acceptable monosaccharides and disaccharides, inan amount of at least 25% by weight of the powder mixture; and anabsorbent agent which forms a bioabsorbable biocompatible matrix withwound secretions, comprising a polymer formed of one or more ofsaccharide or saccharide derivative monomers and lactic acid monomers,in an amount of at least 25% by weight of the powder mixture.

It is another object of the invention to provide a method for healing awound on skin or mucous membranes, comprising administering apharmaceutically acceptable powder to the wound comprising a sugarselected from the group consisting of one or more pharmaceuticallyacceptable monosaccharides and disaccharides, in an amount of at least25% by weight of the powder mixture; and an absorbent agent which formsa bioabsorbable biocompatible matrix with wound secretions, comprising apolymer formed of one or more of saccharide or saccharide derivativemonomers and lactic acid monomers, in an amount of at least 25% byweight of the powder mixture, the powder being provided in sufficientquantity to form a cake on the wound from wound secretions and thepowder.

The sugar may be present in an amount of at least 40% by weight and saidabsorbent agent is present in an amount of at least 40% by weight. In apreferred formulation, the sugar is present in an amount of about 50% byweight and the absorbent agent is present in an amount of about 50% byweight.

The sugar preferably comprises a finely powdered sucrose, e.g., 10×confectioner's sugar.

The absorbent agent preferably comprises cornstarch. The absorbent agentmay also comprise polylactic acid, or a combination of starch andpolylactic acid. Other absorbent agents may also be used, as are knownin the art. A preferred starch is cornstarch.

The wound healing powder may be provided in a dissolvable capsule, e.g.,a gelatin capsule, which holds at least 0.5 gram of powder, and morepreferably 1 gram of powder.

While various descriptions of the present invention are described above,it should be understood that the various features can be used singly orin any combination thereof. Therefore, this invention is not to belimited to only the specifically preferred embodiments depicted herein.

Further, it should be understood that variations and modificationswithin the spirit and scope of the invention may occur to those skilledin the art to which the invention pertains.

Accordingly, all expedient modifications readily attainable by oneversed in the art from the disclosure set forth herein that are withinthe scope and spirit of the present invention are to be included asfurther embodiments of the present invention. The scope of the presentinvention is accordingly defined as set forth in the appended claims.

What is claimed is:
 1. A pharmaceutically acceptable dry powderformulation adapted for administration to external wounds of the skinwhich have wound secretions, to promote tissue regeneration andfunctional microvasculature, comprising: a first component comprising asufficient amount of one or more pharmaceutically acceptablemonosaccharides or disaccharides to form and maintain an antibacterialenvironment resulting from a low water activity and a high osmoticpressure due to partial dissolution of the first component; and a secondcomponent comprising at least one of a starch and polylactic acid,forming a biocompatible and bioabsorbable matrix, wherein thepharmaceutically acceptable dry powder is adapted to adhere and cake onthe external surface of the wound, and to absorb would secretions fromthe wound.
 2. The pharmaceutically acceptable dry powder formulationaccording to claim 1, comprising polylactic acid.
 3. Thepharmaceutically acceptable dry powder formulation according to claim 1,comprising cornstarch.
 4. The pharmaceutically acceptable dry powderformulation according to claim 1, comprising finely granulated sucrose.5. The pharmaceutically acceptable dry powder formulation according toclaim 1, wherein the first component comprises at least 25% by weight.6. The pharmaceutically acceptable dry powder formulation according toclaim 1, wherein the second component comprises at least 25% by weight.7. The pharmaceutically acceptable dry powder formulation according toclaim 1, wherein the first component comprises at least 40% by weight.8. The pharmaceutically acceptable dry powder formulation according toclaim 1, wherein the second component comprises at least 40% by weight.9. The pharmaceutically acceptable dry powder formulation according toclaim 1, wherein the first component comprises at least 25% by weight ofsucrose and the second component comprises at least 25% by weight ofcornstarch.
 10. The pharmaceutically acceptable dry powder formulationaccording to claim 1, wherein the first component comprises at least 40%by weight of sucrose and the second component comprises at least 40% byweight of cornstarch.
 11. The pharmaceutically acceptable dry powderformulation according to claim 1, wherein the first component comprisesat least 25% by weight 10× sugar and the second component comprises atleast 25% by weight cornstarch.
 12. The pharmaceutically acceptable drypowder formulation according to claim 1, further comprising gelatin. 13.A pharmaceutically acceptable dry powder formulation adapted foradministration to the skin, comprising: a sufficient amount of one ormore pharmaceutically acceptable monosaccharides or disaccharides toabsorb would secretions from the wound to form and maintain anantibacterial environment proximate to the wound resulting from a lowwater activity and a high osmotic pressure due to hydration of the oneor more pharmaceutically acceptable monosaccharides or disaccharideswith wound secretions; and a sufficient amount of at least one of astarch and polylactic acid, which is adapted to form a biocompatible andbioabsorbable matrix proximate to the wound to facilitate tissueregeneration, the dry powder being adapted to adhere and cake on theexternal surface of the wound, forming a self-adherent dressing.
 14. Thepharmaceutically acceptable dry powder formulation according to claim13, comprising sucrose and cornstarch.
 15. The pharmaceuticallyacceptable dry powder formulation according to claim 13, wherein thepharmaceutically acceptable monosaccharides or disaccharides comprise atleast 25% by weight, and the at least one of starch and polymactic acidcomprises at least 25% by weight.
 16. The pharmaceutically acceptabledry powder formulation according to claim 13, wherein thepharmaceutically acceptable monosaccharides or disaccharides comprise atleast 40% by weight, and the at least one of starch and polymactic acidcomprises at least 40% by weight.
 17. The pharmaceutically acceptabledry powder formulation according to claim 13, comprising at least 40% byweight of 10× sugar.
 18. A method of treating a wound, comprising:administering the pharmaceutically acceptable dry powder formulationaccording to claim 1 to a wound having wound secretions for form aself-adherent cake on the wound; hydrating a portion of the firstcomponent to result in a low water activity and a high osmotic pressurewith wound secretions to form and maintain an antibacterial environment;forming a biocompatible and bioabsorbable matrix proximate to the woundfrom the second component, to facilitate tissue regeneration; andrepeating administration after a period of time.
 19. The methodaccording to claim 18, wherein the pharmaceutically acceptable drypowder formulation causes a reduction in pH to approximately
 5. 20. Themethod according to claim 18, wherein the first component comprises atleast 40% by weight of sucrose and the second component comprises atleast 40% by weight of cornstarch.